Tuberculosis in the European Region.

Purpose of Review: Tuberculosis (TB) remains a major public health concern worldwide. The COVID-19 pandemic and migration flow due to socioeconomic conditions, climate change, and geopolitical issues, such as the war, are important drivers influencing TB epidemiology in Europe. This article aims to review the data about TB in this area and the new findings about treatment and prevention strategies. Recent Findings: During the COVID-19 pandemic, access to health facilities and retention in care were difficult for TB patients, with consequences on TB diagnosis and TB incidence. The ongoing conflict in Europe, in areas with high prevalence of TB and MDR-TB, has reduced the access to health services and the availability of anti-TB drugs and increased the migration of refugees. New data on short treatment regimens could change the length of therapy and adverse events. Summary: TB control programs are facing emerging challenges that could change TB incidence in the near future. Novel antibiotic strategies and improved preventive policies could offer new opportunities to reduce the TB impact on public health.

Multidrug-resistant gram-negative bacteria in patients with COVID-19: An epidemiological and clinical study.

Epidemiological data regarding the incidence of secondary multidrug-resistant (MDR) Gram-negative infection in patients with coronavirus disease (COVID-19) in Brazil are still ambiguous. Thus, a case-control study was designed to determine factors associated with the acquisition of MDR Gram-negative bacteria (GNB) in patients with and without COVID-19 and describe the mortality rates and clinical features associated with unfavorable outcomes. In total, we assessed 280 patients admitted to Brazilian intensive care units from March/2020 to December/2021. During the study, 926 GNB were isolated. Out of those, 504 were MDR-GNB, representing 54.4% of the resistance rate. In addition, out of 871 patients positive for COVID-19, 73 had secondary MDR-GNB infection, which represented 8.38% of documented community-acquired GNB-MDR infections. The factors associated with patients COVID-19-MDR-GNB infections were obesity, heart failure, use of mechanical ventilation, urinary catheter, and previous use of ß-lactams. Several factors associated with mortality were identified among patients with COVID-19 infected with MDR-GNB, including the use of a urinary catheter; renal failure; and the origin of bacterial cultures such as tracheal secretion, exposure to carbapenem antibiotics, and polymyxin. Mortality was significantly higher in patients with COVID-19-MDR-GNB (68.6%) compared to control groups, where COVID-19 was 35.7%, MDR-GNB was 50%, and GNB was 21.4%. Our findings demonstrate that MDR-GNB infection associated with COVID-19 has an expressive impact on increasing the case fatality rate, reinforcing the importance of minimizing the use of invasive devices and prior exposure to antimicrobials to control the bacterial spread in healthcare environments to improve the prognosis among critical patients.

A pandemic within a pandemic? Admission to COVID-19 wards in hospitals is associated with increased prevalence of antimicrobial resistance in two African settings.

BACKGROUND: Patients who develop severe illness due to COVID-19 are more likely to be admitted to hospital and acquire bacterial co-infections, therefore the WHO recommends empiric treatment with antibiotics. Few reports have addressed the impact of COVID-19 management on emergence of nosocomial antimicrobial resistance (AMR) in resource constrained settings. This study aimed to ascertain whether being admitted to a COVID-19 ward (with COVID-19 infection) compared to a non-COVID-19 ward (as a COVID-19 negative patient) was associated with a change in the prevalence of bacterial hospital acquired infection (HAI) species or resistance patterns, and whether there were differences in antimicrobial stewardship (AMS) and infection prevention and control (IPC) guidelines between COVID-19 and non-COVID-19 wards. The study was conducted in Sudan and Zambia, two resource constrained settings with differing country-wide responses to COVID-19. METHODS: Patients suspected of having hospital acquired infections were recruited from COVID-19 wards and non-COVID-19 wards. Bacteria were isolated from clinical samples using culture and molecular methods and species identified. Phenotypic and genotypic resistance patterns were determined by antibiotic disc diffusion and whole genome sequencing. Infection prevention and control guidelines were analysed for COVID-19 and non-COVID-19 wards to identify potential differences. RESULTS: 109 and 66 isolates were collected from Sudan and Zambia respectively. Phenotypic testing revealed significantly more multi-drug resistant isolates on COVID-19 wards in both countries (Sudan p = 0.0087, Zambia p = 0.0154). The total number of patients with hospital acquired infections (both susceptible and resistant) increased significantly on COVID-19 wards in Sudan, but the opposite was observed in Zambia (both p = ≤ 0.0001). Genotypic analysis showed significantly more ß-lactam genes per isolate on COVID-19 wards (Sudan p = 0.0192, Zambia p = ≤ 0.0001). CONCLUSIONS: Changes in hospital acquired infections and AMR patterns were seen in COVID-19 patients on COVID-19 wards compared to COVID-19 negative patients on non-COVID-19 wards in Sudan and Zambia. These are likely due to a potentially complex combination of causes, including patient factors, but differing emphases on infection prevention and control, and antimicrobial stewardship policies on COVID-19 wards were highlighted.

Evaluation of Virtual Nutrition Counseling as a Nutrition Care and Educational Tool

Structured Supervised Practice (SSP) is an essential component of the undergraduate BS degree program in Human Nutrition and Dietetics because it develops core competencies in entry level dietitians in clinical settings. During Covid-19 pandemic, the Rana Liaquat Ali Khan College of Home Economics (RLAK CHE), Karachi-Pakistan offered virtual internships to the dietetics internes to provide training under the supervision of experienced Dietitians and also save the timeline of their degree program. This study aims to assess the usefulness of virtual clinics in providing understanding of nutrition counselling process to the dietetic internes. Net Promoter Score (NPS) was used to assess the students' acceptability and overall satisfaction levels of students, Dietitians and clients with these virtual clinics. A total of 37 students participated in this internship program. The results of this study showed that acceptability of the program among students is highly favorable (NPS score=42.9). The students were highly satisfied with the various aspects of virtual clinic program as indicated by the NPS (46.5-75.0). Dietitians were also very satisfied (NPS= 53.85-76.92) with this program and its different aspects including trainees responsiveness (SS=76.92), their patients counselling abilities (SS=69.23) and smoothness of the sessions but their satisfaction level was low in sharing their diet plans through screen shares (46.7). The clients' satisfaction level scored extremely satisfied (65.4-96.2). Our results also revealed the usefulness of these clinics to the students after one year of completion when they employed as nutritionist and dietitian in clinics. It was concluded from this study that these virtual nutrition clinic acts as a useful tool not only for educational purpose for students but also for clients to receive nutritional counseling in various circumstances where physical visit is a problem. © 2022,Pakistan Journal of Life and Social Sciences.All Rights Reserved.

Synthesis of bee venom loaded chitosan nanoparticles for anti-MERS-COV and multi-drug resistance bacteria.

This study aims to fully exploit the natural compound; bee venom (BV) as a substance that can kill and inhibit the growth of microbes and viruses. For this target, BV was loaded onto a safe, natural, and economically inexpensive polymer, which is chitosan (Ch) in its nano-size form using the ionic gelation method and chemical crosslinking agent (sodium tripolyphosphate; TPP). The findings illustrated that chitosan nanoparticles (ChNPs) were prepared thru this method exhibited spherical shape and average hydrodynamic size of 202 nm with a polydispersity index (PDI = 0.44). However, the size was increased to 221 nm and PDI (0.37) when chitosan nanoparticles were loaded with BV (ChNC). In addition, the particles of BV appeared as a core and chitosan nanoparticles as a shell implying the successful preparation of nanocomposite (ChNC) that based on the. Encapsulation of BV into ChNPs with significantly small size distribution and good stability that protect these formed nanocomposites from agglomeration. The cytopathic effect (CPE) inhibition assay was used to identify potential antivirals for Middle East respiratory syndrome coronavirus (MERS-CoV). The response of the dose study was designed to influence the range of effectiveness for the chosen antiviral, i.e., the 50 % inhibitory concentration (IC50), as well as the range of cytotoxicity (CC50). However, our results indicated that crude BV had mild anti-MERS-COV with SI = 4.6, followed by ChNPs that exhibited moderate anti-MERS-COV with SI = 8.6. Meanwhile. The nanocomposite of ChNC displayed a promising anti-MERS-COV with SI = 12.1. Additionally, the synthesized nanocomposite (ChNC) had greater antimicrobial activity against both Gram-positive and Gram-negative bacteria when compared with ChNPs, BV or the utilized model drug.

Incidence and Microbiology of Hospital-Acquired Infections in COVID-19 Patients between the First and the Second Outbreak of the SARS-CoV-2 Pandemic: A Retrospective, Observational Study.

With almost 638 million cases and over 6 million deaths worldwide, the SARS-CoV-2 pandemic represents an unprecedented healthcare challenge. Although the management and natural history of COVID-19 patients have changed after the introduction of active therapies and vaccination, the development of secondary infections complicates hospital stay. This is a single-center, retrospective, observational study that explores the incidence and microbiology of hospital-acquired infections (HAIs) in two subsequent populations of hospitalized patients with COVID-19. Demographic, pre-hospitalization baseline characteristics, therapeutic options and microbiology data about secondary infections were collected for a total of 1153 cases. The second population appeared to have a higher median age (73 vs. 63 years, respectively), comorbidities (median Charlson Comorbidity Index Score was 4 vs. 1, respectively) and incidence of secondary infections (23.5% vs. 8.2%) with respect to the first. A higher incidence of multi-drug resistant organisms (MDROs), including difficult-to-treat resistant (DTR) Pseudomonas, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), was also observed. Both patients' characteristics and poor adherence to standard hygiene and infection control protocols may have contributed to the higher incidence of these events and may have impacted on the natural history of the disease. In-hospital mortality rates were similar, despite the introduction of active therapies against COVID-19 (24.7% vs. 23.5%, respectively). The incidence of HAIs may have contributed to the unchanged mortality and prompts for more effective antimicrobial stewardship and infection control procedures in COVID-19.

Is It Possible to Eradicate Carbapenem-Resistant Acinetobacter baumannii (CRAB) from Endemic Hospitals?

BACKGROUND: Despite the global efforts to antagonize carbapenem-resistant Acinetobacter baumannii (CRAB) spreading, it remains an emerging threat with a related mortality exceeding 40% among critically ill patients. The purpose of this review is to provide evidence concerning the best infection prevention and control (IPC) strategies to fight CRAB spreading in endemic hospitals. METHODS: The study was a critical review of the literature aiming to evaluate all available studies reporting IPC measures to control CRAB in ICU and outside ICU in both epidemic and endemic settings in the past 10 years. RESULTS: Among the 12 included studies, the majority consisted of research reports of outbreaks mostly occurred in ICUs. The reported mortality reached 50%. Wide variability was observed related to the frequency of application of recommended CRAB IPC measures among the studies: environmental disinfection (100%); contact precautions (83%); cohorting staff and patients (75%); genotyping (66%); daily chlorhexidine baths (58%); active rectal screening (50%); closing or stopping admissions to the ward (33%). CONCLUSIONS: Despite effective control of CRAB spreading during the outbreaks, the IPC measures reported were heterogeneous and highly dependent on the different setting as well as on the structural characteristics of the wards. Reinforced 'search and destroy' strategies both on the environment and on the patient, proved to be the most effective measures for permanently eliminating CRAB spreading.

Tuberculosis Phenotypic and Genotypic Drug Susceptibility Testing and Immunodiagnostics: A Review.

Tuberculosis (TB), considered an ancient disease, is still killing one person every 21 seconds. Diagnosis of Mycobacterium tuberculosis (M.tb) still has many challenges, especially in low and middle-income countries with high burden disease rates. Over the last two decades, the amount of drug-resistant (DR)-TB cases has been increasing, from mono-resistant (mainly for isoniazid or rifampicin resistance) to extremely drug resistant TB. DR-TB is problematic to diagnose and treat, and thus, needs more resources to manage it. Together with+ TB clinical symptoms, phenotypic and genotypic diagnosis of TB includes a series of tests that can be used on different specimens to determine if a person has TB, as well as if the M.tb strain+ causing the disease is drug susceptible or resistant. Here, we review and discuss advantages and disadvantages of phenotypic vs. genotypic drug susceptibility testing for DR-TB, advances in TB immunodiagnostics, and propose a call to improve deployable and low-cost TB diagnostic tests to control the DR-TB burden, especially in light of the increase of the global burden of bacterial antimicrobial resistance, and the potentially long term impact of the coronavirus disease 2019 (COVID-19) disruption on TB programs.

Use of CRISPR in Infection Control.

One of the greatest threats to the global world is infectious diseases. The morbidity and fatality of infectious diseases cause 17 million deaths annually. The recent COVID-19 pandemic describes the uncertain potential of these diseases. Understanding the pathogenesis of infectious agents, including bacteria, viruses, fungi, etc. and the evolution of rapid diagnostic techniques and treatments has become a pressing priority to improve infectious disease outcomes worldwide. Clustered regularly interspaced short palindromic repeats (CRISPR) constitute the adaptive immune system of archaea and bacteria along with CRISPR-associated (Cas) proteins that recognize and destroy foreign DNA acting as molecular scissors. Since their discovery, CRISPR systems are classified into 6 types and 22 subtypes. Type II, V, and VI are used for diagnostic purposes. Utilizing the CRISPR-Cas system's capabilities will aid promote the development of novel and improved diagnostics as well as innovative delivery systems and the prevention and treatment of infectious diseases.

Fungal Bloodstream Co-infection by Trichosporon asahii in a COVID-19 Critical Patient: Case Report and Literature Review.

Opportunistic infections are serious complications in critically ill COVID-19 patients, especially co-infections with bacterial and fungal agents. Here we report a rare case of bloodstream co-infection by Trichosporon asahii, an emerging yeast, and Acinetobacterbaumannii, an opportunistic nosocomial pathogen, both multidrug resistant, in a tertiary hospital from southern Brazil. A review of the literature regarding similar cases is also included. Treatment with multiple antimicrobials failed, and the patient progressed to death four days after the diagnosis of bacteremia and fungemia.

The Spread of NDM-1 and NDM-7-Producing Klebsiella pneumoniae Is Driven by Multiclonal Expansion of High-Risk Clones in Healthcare Institutions in the State of Pará, Brazilian Amazon Region.

Carbapenem resistance among Klebsiella pneumoniae isolates is often related to carbapenemase genes, located in genetic transmissible elements, particularly the blaKPC gene, which variants are spread in several countries. Recently, reports of K. pneumoniae isolates harboring the blaNDM gene have increased dramatically along with the dissemination of epidemic high-risk clones (HRCs). In the present study, we report the multiclonal spread of New Delhi metallo-beta-lactamase (NDM)-producing K. pneumoniae in different healthcare institutions in the state of Pará, Northern Brazil. A total of 23 NDM-producing isolates were tested regarding antimicrobial susceptibility testing features, screening of carbapenemase genes, and genotyping by multilocus sequencing typing (MLST). All K. pneumoniae isolates were determined as multidrug-resistant (MDR), being mainly resistant to carbapenems, cephalosporins, and fluoroquinolones. The blaNDM-7 (60.9%-14/23) and blaNDM-1 (34.8%-8/23) variants were detected. MLST genotyping revealed the predomination of HRCs, including ST11/CC258, ST340/CC258, ST15/CC15, ST392/CC147, among others. To conclude, the present study reveals the contribution of HRCs and non-HRCs in the spread of NDM-1 and NDM-7-producing K. pneumoniae isolates in Northern (Amazon region) Brazil, along with the first detection of NDM-7 variant in Latin America and Brazil, highlighting the need for surveillance and control of strains that may negatively impact healthcare and antimicrobial resistance.

Phage therapeutics: from promises to practices and prospectives.

The rise in multi-drug resistant bacteria and the inability to develop novel antibacterial agents limits our arsenal against infectious diseases. Antibiotic resistance is a global issue requiring an immediate solution, including the development of new antibiotic molecules and other alternative modes of therapy. This article highlights the mechanism of bacteriophage treatment that makes it a real solution for multidrug-resistant infectious diseases. Several case reports identified phage therapy as a potential solution to the emerging challenge of multi-drug resistance. Bacteriophages, unlike antibiotics, have special features, such as host specificity and do not impact other commensals. A new outlook has also arisen with recent advancements in the understanding of phage immunobiology, where phages are repurposed against both bacterial and viral infections. Thus, the potential possibility of phages in COVID-19 patients with secondary bacterial infections has been briefly elucidated. However, significant obstacles that need to be addressed are to design better clinical studies that may contribute to the widespread use of bacteriophage therapy against multi-drug resistant pathogens. In conclusion, antibacterial agents can be used with bacteriophages, i.e. bacteriophage-antibiotic combination therapy, or they can be administered alone in cases when antibiotics are ineffective.Key points• AMR, a consequence of antibiotic generated menace globally, has led to the resurgence of phage therapy as an effective and sustainable solution without any side effects and high specificity against refractory MDR bacterial infections.• Bacteriophages have fewer adverse reactions and can thus be used as monotherapy as well as in conjunction with antibiotics.• In the context of the COVID-19 pandemic, phage therapy may be a viable option.

Multi-Drug Resistance Bacterial Infections in Critically Ill Patients Admitted with COVID-19.

INTRODUCTION: It is known that bacterial infections represent a common complication during viral respiratory tract infections such as influenza, with a concomitant increase in morbidity and mortality. Nevertheless, the prevalence of bacterial co-infections and secondary infections in critically ill patients affected by coronavirus disease 2019 (COVID-19) is not well understood yet. We performed a review of the literature currently available to examine the incidence of bacterial secondary infections acquired during hospital stay and the risk factors associated with multidrug resistance. Most of the studies, mainly retrospective and single-centered, highlighted that the incidence of co-infections is low, affecting about 3.5% of hospitalized patients, while the majority are hospital acquired infections, developed later, generally 10-15 days after ICU admission. The prolonged ICU hospitalization and the extensive use of broad-spectrum antimicrobial drugs during the COVID-19 outbreak might have contributed to the selection of pathogens with different profiles of resistance. Consequently, the reported incidence of MDR bacterial infections in critically ill COVID-19 patients is high, ranging between 32% to 50%. MDR infections are linked to a higher length of stay in ICU but not to a higher risk of death. The only risk factor independently associated with MDR secondary infections reported was invasive mechanical ventilation (OR 1.062; 95% CI 1.012-1.114), but also steroid therapy and prolonged length of ICU stay may play a pivotal role. The empiric antimicrobial therapy for a ventilated patient with suspected or proven bacterial co-infection at ICU admission should be prescribed judiciously and managed according to a stewardship program in order to interrupt or adjust it on the basis of culture results.

Present and Future Perspectives on Therapeutic Options for Carbapenemase-Producing Enterobacterales Infections.

Carbapenem-resistant Enterobacterales (CRE) are included in the list of the most threatening antibiotic resistance microorganisms, being responsible for often insurmountable therapeutic issues, especially in hospitalized patients and immunocompromised individuals and patients in intensive care units. The enzymatic resistance to carbapenems is encoded by different ß-lactamases belonging to A, B or D Ambler class. Besides compromising the activity of last-resort antibiotics, CRE have spread from the clinical to the environmental sectors, in all geographic regions. The purpose of this review is to present present and future perspectives on CRE-associated infections treatment.

Clinical characteristics and risk factors for the isolation of multi-drug-resistant Gram-negative bacteria from critically ill patients with COVID-19.

BACKGROUND: We investigated the clinical characteristics and risk factors for the isolation of multi-drug-resistant (MDR) Gram-negative bacteria (GNB) from critically ill COVID-19 patients. METHODS: We retrospectively matched (1:2) critical COVID-19 patients with one or more MDR GNB from any clinical specimen (cases), with those with no MDR GNB isolates (controls). RESULTS: Seventy-eight cases were identified (4.5 per 1000 intensive care unit (ICU) days, 95% confidence interval (CI) 3.6-5.7). Of 98 MDR GNB isolates, the most frequent species were Stenotrophomonas maltophilia (24, 24.5%), and Klebsiella pneumoniae (23, 23.5%). Two (8.7%) K. pneumoniae, and six (85.7%) Pseudomonas aeruginosa isolates were carbapenem resistant. A total of 24 (24.5%) isolates were not considered to be associated with active infection. Those with active infection received appropriate antimicrobial agents within a median of one day. The case group had significantly longer median central venous line days, mechanical ventilation days, and hospital length of stay (P<0.001 for each). All-cause mortality at 28 days was not significantly different between the two groups (P=0.19). Mechanical ventilation days (adjusted odds ratio 1.062, 95% CI 1.012-1.114; P=0.015), but not receipt of corticosteroids or tocilizumab, was independently associated with the isolation of MDR GNB. There was no association between MDR GNB and 28-day all-cause mortality (adjusted odds ratio 2.426, 95% CI 0.833-7.069; P= 0.104). CONCLUSION: In critically ill COVID-19 patients, prevention of MDR GNB colonization and infections requires minimizing the use of invasive devices, and to remove them as soon as their presence is no longer necessary.

Acinetobacter baumannii: Its Clinical Significance in Human and Veterinary Medicine.

Acinetobacter baumannii is a Gram-negative, opportunistic pathogen, causing severe infections difficult to treat. The A. baumannii infection rate has increased year by year in human medicine and it is also considered as a major cause of nosocomial infections worldwide. This bacterium, also well known for its ability to form biofilms, has a strong environmental adaptability and the characteristics of multi-drug resistance. Indeed, strains showing fully resistant profiles represent a worrisome problem in clinical therapeutic treatment. Furthermore, A. baumannii-associated veterinary nosocomial infections has been reported in recent literature. Particularly, carbapenem-resistant A. baumannii can be considered an emerging opportunistic pathogen in human medicine as well as in veterinary medicine.

Molecular basis of the beta-lactamase protein using comparative modelling, drug screening and molecular dynamics studies to understand the resistance of ß-lactam antibiotics.

Beta-lactamase (ampC) in general causes the onset of antibiotic resistance in pathogenic bacteria against the ß-lactam antibiotics. Morganella morganii which belongs to the Proteae tribe of the Enterobacteriaceae family is a Gram-negative bacillus. Gram-negative bacteria are the key problematic agents among the human population in overexpressing resistance against ß-lactam antibiotics. These ß-lactam antibiotics being experimentally well studied still lack the key information and mechanism for their resistance. The structural information of the ampC protein is unknown and poorly studied; hence, it is the need of the hour to find effective inhibitors against it. In our study, the prediction of the three-dimensional structure of ampC protein from Morganella morganii was performed using a comparative modelling approach. The predicted structure was energetically stabilized and functional conformations were mapped through 100-ns molecular dynamics simulation runs. Also, Ramachandran plot shows the model to be stereo-chemically stable with most residues found under core allowed regions. Drug screening with several experimentally tested inhibitors was then confirmed to check the activity against ampC protein using an AutoDock tool. The results suggested OncoglabrinolC molecule as the best inhibitor (out of 21 drug molecules) with a binding affinity of - 11.44 kcal/mol. Anti-bacterial/anti-parasitic inhibitors have not only been used against bacterial infections, but later reports have also shown them to work against deadly viruses such as SARS-CoV2. This key structural and inhibitory information is certain to help in the discovery of specific and potent substitute therapeutic drugs and the development of experimental procedures against human infection.

Complex dynamics in susceptible-infected models for COVID-19 with multi-drug resistance.

Nowadays, exploring complex dynamic of epidemic models becomes a focal point for research after the outbreak of COVID-19 pandemic which has no vaccine or fully approved drug treatment up till now. Hence, complex dynamics in a susceptible-infected (SI) model for COVID-19 with multi-drug resistance (MDR) and its fractional-order counterpart are investigated. Existence of positive solution in fractional-order model is discussed. Local stability based on the fractional Routh-Hurwitz (FRH) conditions is considered. Also, new FRH conditions are introduced and proved for the fractional case (0,2]. All these FRH conditions are also applied to discuss local stability of the multi-drug resistance steady states. Chaotic attractors are also found in this model for both integer-order and fractional-order cases. Numerical tools such as Lyapunov exponents, Lyapunov spectrum and bifurcation diagrams are employed to confirm existence of these complex dynamics. This study helps to understand complex behaviors and predict spread of severe infectious diseases such as COVID-19.